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Objectives: This meta-analysis evaluated the Efficacy and Effectiveness of several COVID-19 vaccines, including AstraZeneca, Pfizer, Moderna, Bharat, and Johnson & Johnson, to better estimate their immunogenicity, benefits, or side effects. Methods: Studies reporting the Efficacy and Effectiveness of COVID-19 vaccines from November 2020 to April 2022 were included. The pooled Effectiveness/Efficacy with a 95% confidence interval (95% CI) with Metaprop order was calculated. The results were presented in forest plots. Predefined subgroup analyses and sensitivity analyses were also performed. Results: A total of twenty articles were included in this meta-analysis. After the first dose of the vaccine, the total effectiveness of all COVID-19 vaccines in our study was 71% (95% CI 0.65, 0.78). The total effectiveness of vaccines after the second dose was 91% (95% CI 0.88, 0.94)). The total efficacy of vaccines after the first and second doses was 81% (95% CI 0.70, 0.91) and 71% (95% CI 0.62, 0.79), respectively. The effectiveness of the Moderna vaccine after the first and second dose was the highest among other studied vaccines ((74% (95% CI, 0.65, 0.83) and 93% (95% CI, 0.89, 0.97), respectively). The highest first dose overall effectiveness of the studied vaccines was against the Gamma variant (74% (95% CI, 0.73, 0.75)), and the highest effectiveness after the second dose was observed against the Beta variant (96% (95% CI, 0.96, 0.96)). The Efficacy for AstraZeneca and Pfizer vaccines after the first dose was 78% (95% CI, 0.62, 0.95) and 84% (95% CI, 0.77, 0.92), respectively. The second dose Efficacy for AstraZeneca, Pfizer, and Bharat was 67% (95% CI, 0.54, 0.80), 93% (95% CI, 0.85, 1.00), and 71% (95% CI, 0.61, 0.82), respectively. The overall efficacy of first and second dose vaccination against the Alfa variant was 84% (95% CI, 0.84, 0.84) and 77% (95% CI, 0.57, 0.97), respectively, the highest among other variants. Conclusion: mRNA-based vaccines against COVID-19 showed the highest total efficacy and effectiveness than other vaccines. In general, administering the second dose produced a more reliable response and higher effectiveness than a single dose. [ABSTRACT FROM AUTHOR]

This study assessed safety and immunogenicity of Serum Institute of India Pvt Ltd (SIIPL)'s tetanus toxoid (TT), diphtheria toxoid (DT), and acellular pertussis booster vaccine (Tdap). In this Phase II/III, multicenter, randomized, active-controlled, open-label study, 1500 healthy individuals, aged 4–65 years, were randomized to receive a single dose of SIIPL Tdap or comparator Tdap vaccine (Boostrix®; GlaxoSmithKlines, India). Adverse events (AEs) during initial 30 minutes, 7-day, 30-day post-vaccination were assessed. Blood samples were taken before and 30 days post-vaccination for immunogenicity assessment. No significant differences in incidence of local and systemic solicited AEs were observed between the two groups; no vaccine-related serious AEs were reported. SIIPL Tdap was non-inferior to comparator Tdap in achieving booster responses to TT and DT in 75.2% and 70.8% of the participants, respectively, and to pertussis toxoid (PT), pertactin (PRN), and filamentous hemagglutinin (FHA) in 94.3%, 92.6%, and 95.0% of the participants, respectively. Anti-PT, anti-PRN, and anti-FHA antibody geometric mean titers in both the groups, were significantly higher post-vaccination compared to pre-vaccination. Booster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to immunogenicity against tetanus, diphtheria, and pertussis and was well tolerated. [ABSTRACT FROM AUTHOR]

Yellow fever, a mosquito-borne flavivirus infection, is an important public health problem in Africa and Latin America. A Yellow Fever vaccine (YFV) was developed and tested in a study in India. This was a Phase I, open-label, randomized, controlled study where healthy adults received SII YFV intramuscularly (SII YFV IM), SII YFV subcutaneously (SII YFV SC) or STAMARIL® (Sanofi-Pasteur) in 1:1:1 ratio. They were followed for solicited reactions for 10 days and unsolicited events for 28 days and serious adverse events for 3 months. YF-neutralizing antibodies were measured at baseline and on Days 10, 14, 28. A total of 60 adults were enrolled in the study. The proportion of participants with solicited reactions was 10%, 40%, and 25% in SII YFV SC, SII YFV IM, and STAMARIL® arms, respectively. No causally related unsolicited events or any serious adverse event was reported. After vaccination, the seroconversion was 94.44%, 100%, and 100%, in the three arms respectively. The post-vaccination geometric mean titers were similar in the study arms. The new YFV was found safe and immunogenic by IM as well as SC routes. The vaccine can be tested in further phases of clinical studies. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the persistence of antibodies three years after primary vaccination with typhoid conjugate vaccine (TCV) of either Cadila Healthcare Ltd. (Cadila-TCV) or Bharat Biotech International Ltd. (Bharat-TCV) administered in a previous phase II/III study, and to study the booster dose response to Cadila-TCV. Methods: This was an open-label, phase IV extension study conducted in tertiary care and multispecialty hospitals in India. 112 subjects (Cadila-TCV-57, Bharat-TCV-55) who had participated in previous study were enrolled. Of these, eligible subjects received a single-dose of Cadila-TCV and were followed-up for 28 days post-booster. Primary outcome was persistence of antibodies 3 years after primary vaccination and seroconversion (≥4-fold rise in antibody titre from baseline) 28 days post-booster. Safety was based on reported adverse events (AEs) post-booster. Results: The baseline GMT reported in the current study was significantly higher than pre-vaccination GMT reported in the previous study. 89/112 (79.5%) subjects had antibody titer ≥10 IU/mL at baseline; eligible subjects (n=17) who had baseline antibody titre <10 IU/mL were administered booster dose. All the vaccinated subjects showed seroconversion post-booster. The GMTs reported at 10 days and 28 days post-booster were significantly higher as compared to GMTs reported after primary vaccination in previous study. 4 (23.5%) vaccinated subjects reported 9 AEs; all were solicited and of mild/moderate intensity. Conclusion: There was a significant persistence of immunogenicity after primary vaccination with both the TCVs, and robust immune response after booster vaccination with Cadila-TCV. [ABSTRACT FROM AUTHOR]

The subterranean termite Odontotermes obesus is an important pest of the Indian subcontinent, causing extensive damage to major agricultural crops and forest plantation trees. Control of termites by strategies employing their parasites has limitations because they have evolved a complex social structure, immune responses, and adaptive behavior toward pathogen-infected individuals. Nonparasitic rhizobacteria that produce harmful metabolites might facilitate the biocontrol of termites. In the present investigation, three different species of hydrogen cyanide-producing rhizobacteria were tested for their potential to kill O. obesus. The three bacterial species were found to be effective in killing the termites under in vitro conditions. [ABSTRACT FROM AUTHOR]

The prevalence of iron (Fe) deficiency and subclinical lead (Pb) toxicity is high in developing countries like India, and information on their potential additive effects on immune responses is scant. The current study assessed immune parameters in dual Pb-exposed\Fe-deficient weanling SD rats. Rats were fed a control (CD) or Fe-deficient (ID) diet for 4 weeks and then evaluated for hemoglobin (Hb) and serum Fe status. Then, half the rats in each group began to receive daily oral Pb exposure (25 mg/4 ml/kg BW; gavage) or vehicle for a further 4 weeks (while maintained on original respective diets). After the 4-weeks of dosing, rats were assessed for Hb and serum Fe, and for blood lead level (BLL) and δ-aminolevulinic acid dehydratase (ALAD) activity. At this point, half the rats in each group (now n = 8) were then vaccinated with tetanus toxoid (TT), and then two boosters at 2-week intervals. All the time, rats stayed on their original respective diets along with exposure to Pb on alternate days. At 2 weeks after the final booster, rats were euthanized and blood collected to assess total/specific IgG and IgM levels; mucosal (intestinal) IgA levels were also determined. Spleens were taken to assess CD4+ and CD8+ cell levels and for ex vivo measures of splenocyte proliferation/TH1 and TH2 cytokine formation. The results indicated significant lowering of Hb and serum Fe levels in ID rats and increased blood Pb and decreased ALAD activity in all Pb-exposed rats. Fe-deficiency alone induced significant increases in ALAD activity, but only in an absence of Pb. While there was no impact of any regimen on total or TT-specific IgG, significant decreases in mucosal IgA and TT-specific IgM were seen in ID-fed Pb-exposed rats. CD4+ cell levels were not impacted by treatment; CD8+ levels were increased in all ID/Pb-exposed rats. Ex-vivo splenocyte proliferation was significantly higher among vaccinated rats, as well as ID-fed Pb-exposed unvaccinated rats. Cytokine formation in all cases was highly variable. The results suggest that Fe deficiency compromised cell-mediated, mucosal, and/or humoral immune response-related endpoints and that Pb exposure during the deficiency further impacted these outcomes. [ABSTRACT FROM AUTHOR]

This open-label study assessed the safety and immunogenicity of two doses (14 days apart) of an indigenously manufactured, killed, bivalent (Vibrio cholerae O1 and O139), whole-cell oral cholera vaccine (SHANCHOL; Shantha Biotechnics) in healthy adults (n = 100) and children (n = 100) in a cholera endemic area (Vellore, South India) to fulfill post-licensure regulatory requirements and post-World Health Organization (WHO) prequalification commitments. Safety and reactogenicity were assessed, and seroconversion rates (i.e. proportion of participants with a ≥ 4-fold rise from baseline in serum vibriocidal antibody titers against V. cholerae O1 Inaba, O1 Ogawa and O139, respectively) were determined 14 days after each vaccine dose. No serious adverse events were reported during the study. Commonly reported solicited adverse events were headache and general ill feeling. Seroconversion rates after the first and second dose in adults were 67.7% and 55.2%, respectively, against O1 Inaba; 47.9% and 45.8% against O1 Ogawa; and 19.8% and 20.8% against O139. In children, seroconversion rates after the first and second dose were 80.2% and 68.8%, respectively, against O1 Inaba; 72.9% and 67.7% against O1 Ogawa; and 26.0% and 18.8% against O139. The geometric mean titers against O1 Inaba, O1 Ogawa, and O139 in both adults and children were significantly higher after each vaccine dose compared to baseline titers (P < 0.001; for both age groups after each dose versus baseline). The seroconversion rates for O1 Inaba, O1 Ogawa, and O139 in both age groups were similar to those in previous studies with the vaccine. In conclusion, the killed, bivalent, whole-cell oral cholera vaccine has a good safety and reactogenicity profile, and is immunogenic in healthy adults and children. Trial Registration: ClinicalTrials.gov ; CTRI/2012/01/002354. [ABSTRACT FROM AUTHOR]

Effective vaccine design relies on accurate knowledge of protection against a pathogen, so as to be able to induce relevant and effective protective responses against it. An ideal Human Immunodeficiency virus (HIV) vaccine should induce humoral as well as cellular immune responses to prevent initial infection of host cells or limit early events of viral dissemination. A Phase I HIV-1 prophylactic vaccine trial sponsored by the International AIDS Vaccine Initiative (IAVI) was conducted in India in 2009.The trial tested a HIV-1 subtype C vaccine in a prime-boost regimen, comprising of a DNA prime (ADVAX) and Modified Vaccine Ankara (MVA) (TBC-M4) boost. The trial reported that the vaccine regimen was safe, well tolerated, and resulted in enhancement of HIV-specific immune responses. However, preliminary immunological studies were limited to vaccine-induced IFN-γ responses against the Env and Gag peptides. The present study is a retrospective study to characterize in detail the nature of the vaccine-induced cell mediated immune responses among volunteers, using Peripheral Blood Mononuclear Cells (PBMC) that were archived during the trial. ELISpot was used to measure IFN-γ responses and polyfunctional T cells were analyzed by intracellular multicolor flow cytometry. It was observed that DNA priming and MVA boosting induced Env and Gag specific bi-functional and multi-functional CD4+ and CD8+ T cells expressing IFN-γ, TNF-α and IL-2. The heterologous prime-boost regimen appeared to be slightly superior to the homologous prime-boost regimen in inducing favorable cell mediated immune responses. These results suggest that an in-depth analysis of vaccine-induced cellular immune response can aid in the identification of correlates of an effective immunogenic response, and inform future design of HIV vaccines. [ABSTRACT FROM AUTHOR]

In India the sand fly, Phlebotomus argentipes, transmitted parasitic disease termed kala-azar is caused by Leishmania donovani (LD) in humans. These immune-evading parasites have increasingly developed resistance to the drug sodium antimony gluconate in endemic regions. Lack of early diagnosis methods for the disease limits the information available regarding the early interactions of this parasite with either human tissues or cell lineages. We reasoned that peripheral blood mononuclear cells (PBMCs) from healthy human beings could help compare some of their immune signatures once they were exposed for up to 8 days, to either pentavalent antimony sensitive (SbS-LD) or resistant (SbR-LD) Leishmania donovani isolates. At day 2, PBMC cultures exposed to SbS-LD and SbR-LD stationary phase promastigotes had four and seven fold higher frequency of IL-10 secreting monocyte-macrophage respectively, compared to cultures unexposed to parasites. Contrasting with the CD4+CD25−CD127− type-1 T-regulatory (Tr1) cell population that displayed similar features whatever the culture conditions, there was a pronounced increase in the IL-10 producing CD4+CD25+CD127low/− inducible T-regulatory cells (iTregs) in the PBMC cultures sampled at day 8 post addition of SbR-LD. Sorted iTregs from different cultures on day 8 were added to anti-CD3/CD28 induced naïve PBMCs to assess their suppressive ability. We observed that iTregs from SbR-LD exposed PBMCs had more pronounced suppressive ability compared to SbS-LD counterpart on a per cell basis and is dependent on both IL-10 and TGF-β, whereas IL-10 being the major factor contributing to the suppressive ability of iTregs sorted from PBMC cultures exposed to SbS–LD. Of note, iTreg population frequency value remained at the basal level after addition of genetically modified SbR-LD lacking unique terminal sugar in surface glycan. Even with limitations of this artificial in vitro model of L. donovani-human PBMC interactions, the present findings suggest that SbR-LD have higher immunomodulatory capacity which may favour aggressive pathology. Author Summary: The disease Kala-azar is caused by Leishmania donovani (LD). The disease is characterized by the depression of cellular immune response. In the Indian subcontinent LD parasites are mostly resistant to commonly used antileishmanial drug, like sodium antimony gluconate (SAG). It is known that infection with pentavalent antimony (Sb)-resistant parasites induces aggressive pathology- the cause is still not known. Sb-resistant parasites endowed with unique glycan which may also play an important role in the pathogenesis as following removal of terminal sugar of glycan these parasites behave like sensitive parasites. The diagnosis of the disease is possible after the disease sets in and therefore limited information is available on the host-parasite interaction at the onset of disease. As a surrogate of in vivo scenario we studied the interaction between normal human PBMC with Sb-sensitive and Sb-resistant parasites. The Sb-resistant parasites upon interaction with human peripheral blood mononuclear cells (PBMC) in vitro produced two distinct inhibitory cytokines, IL-10 and TGF-β. Similar experiment with Sb-sensitive LD induced much less amount of above cytokines. Thus aggressive pathology induced by Sb-resistant LD, may be, in part attributed to production of dual inhibitory cytokines where surface glycan of the parasite may play a decisive role. [ABSTRACT FROM AUTHOR]

At the end of 2005, an outbreak of fever associated with joint pain occurred in La Reúnion. The causal agent, chikungunya virus (CHIKV), has been known for 50 years and could thus be readily identified. This arbovirus is present worldwide, particularly in India, but also in Europe, with new variants returning to Africa. In humans, it causes a disease characterized by a typical acute infection, sometimes followed by persistent arthralgia and myalgia lasting months or years. Investigations in the La Reúnion cohort and studies in a macaque model of chikungunya implicated monocytes-macrophages in viral persistence. In this Review, we consider the relationship between CHIKV and the immune response and discuss predictive factors for chronic arthralgia and myalgia by providing an overview of current knowledge on chikungunya pathogenesis. Comparisons of data from animal models of the acute and chronic phases of infection, and data from clinical series, provide information about the mechanisms of CHIKV infection-associated inflammation, viral persistence in monocytes-macrophages, and their link to chronic signs. [ABSTRACT FROM AUTHOR]

Background: The world has recently overcome the first influenza pandemic of the 21st century caused by a novel H1N1 virus (pH1N1) which is a triple reassortant comprising genes derived from avian, human, and swine influenza viruses and antigenically quite different from seasonal H1N1 strains. Although the case fatality rates have decreased in many developed countries, the situation is still alarming in many developing countries including India where considerable numbers of new cases are appearing everyday. There is still a high morbidity and mortality of susceptible adult as well as young population without having underlying health issues due to the influenza infection. Results: To achieve a better understanding of the risk posed by the pH1N1 and to understand its pathogenicity, we studied the host gene expression response to Indian isolate of pH1N1 infection and compared it with seasonal H1N1 infection. The response was studied at four different time points (4, 8, 16 and 24 h) post infection (hpi) in A549 cells using microarray platform. We found that pH1N1 induces immune response earlier than seasonal H1N1 viruses, but at the later stages of infection there is a suppression of host immune responses. The infection with pH1N1 resulted in considerable decrease in the expression of cytokine and other immune genes namely IL8, STAT1, B2 M and IL4 compared to seasonal H1N1. Conclusion: We propose that the inability to induce strong innate immune response could be a reason for the high transmissibility, pathogenicity and mortality caused by pH1N1 virus. [ABSTRACT FROM AUTHOR]

Background: An unusually high number of severe pneumonia cases with considerable mortality is being observed with the pandemic H1N1 2009 virus infections globally. In India, all mild as well as critically ill cases were admitted and treated in the government hospitals during the initial phase of the pandemic. The present study was undertaken during this early phase of the pandemic. Methodology: The role of viral load and host factors in the pathogenesis were assessed by examining 26 mild (MP), 15 critically ill patients (CIP) and 20 healthy controls from Pune, India. Sequential blood and lung aspirate samples were collected from CIP. Viral load and cytokines/chemokine levels were determined from the plasma and lung aspirates of the patients. TLR levels were determined by staining and FACS analysis. Gene profiling was done for both cells in the lung aspirates and PBMCs using TaqMan Low Density arrays. Antibody titres and isotyping was done using HA protein based ELISAs. Principal Findings: 13/15 critically ill patients expired. All plasma samples were negative for the virus irrespective of the patient's category. Sequential lung samples from CIP showed lower viral loads questioning association of viral replication with the severity. Anti-rpH1N1-09-HA-IgG titres were significantly higher in critically ill patients and both categories circulated exclusively IgG1 isotype. Critically ill patients exhibited increase in TLR-3, 4, 7 and decrease in TLR-2 expressions. The disease severity correlated with increased plasma levels of IL1RA, IL2, IL6, CCL3, CCL4 and IL10. Majority of the immune-function genes were down-regulated in the PBMCs and up-regulated in the cells from lung aspirates of critically ill patients. No distinct pattern differentiating fatal and surviving patients was observed when sequential samples were examined for various parameters. Conclusions: Disease severity was associated with pronounced impairment of host immune response. [ABSTRACT FROM AUTHOR]

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Objectives: Hepatitis E virus (HEV) is the predominant cause of water-borne epidemics, sporadic acute viral hepatitis (AVH) in adults and fulminant hepatic failure (FHF) among pregnant women and other adults in India. This preliminary study was designed to examine the association of viral load and certain host immune responses with uneventful recovery or progression to FHF. Methods: Viral load, anti-HEV antibody titers, rORF2p-induced Th1/Th2 cytokines levels and cellular immune responses were assessed in 47 patients with self-limiting hepatitis E and 14 FHF-E cases. The controls included 16 anti-HEV-IgM and IgG-negative healthy individuals. Results: In AVH category, the viral load was 2.4 × 104 ± 1.92 × 104 copies/ml while except for one, all FHF patients were negative for HEV RNA; anti-HEV-IgM and IgG titers were higher in the FHF group. Lymphocyte proliferative response to rORF2p was comparable in both groups. As compared to AVH, significantly higher levels of both Th1 (IFN-γ, IL-2 and TNF-α) and Th2 (IL-10) cytokines were recorded in FHF patients. Analysis of sequential samples differentiated FHF recovered and fatal patients with respect to IFN-γ and IL-12. Conclusion: The results document increased Th1/Th2 responses and anti-HEV titers in FHF patients that warrant in-depth immunological studies. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This study was aimed to assess the prevalence of naturally acquired humoral immune responses and their association with reduced susceptibility to malaria in children and adults with differential clinical conditions from an Indian zone where malaria is endemic. The study was undertaken in an eastern province of India (Keonjhar, Orissa) in a group of 341 children (both younger and older) and 98 adults living in two different areas, Town area and Forest area. They were studied for their parasitological and immunological profiles. Sera from different age-matched groups were screened by ELISA to measure IgG reactivities for characterizing humoral immune responses to the B-cell epitopes of Plasmodium falciparum MSP1, AMA1, RAP1 and EBA175 peptides and P. falciparum-infected erythrocyte lysate. In Town area, overall P. falciparum cases were 5.5%, whereas those in Forest area were 26.7%. We observed an age-wise increasing trend of immunity in these two populations. It was also noticed that the frequency of responders to stage-specific antigens was higher in individuals from the Town area where the frequency of malaria was lower. The naturally acquired humoral immune responses to different stage-specific antigens of P. falciparum reflect the reduced risk of malaria in the study groups. The higher frequency of seroresponders showed correlation with lower risk of developing malaria. [ABSTRACT FROM AUTHOR]

A group comprising 27 young children (1-4y of age) suffering from uncomplicated falciparum malaria were studied to characterize the isolates and to measure humoral immune responses during acute infection and after recovery. Finger prick blood from each individual was collected on d 1. After treatment with chloroquine, a further blood sample was collected from each child on d 7, 30, 90 and 180 for assay of antibody responses to P. falciparum antigens. Isolates from individual patients were incubated in vitro for demonstration of rosette formation, assay of plasmodial growth rate and analysis of Pfcrt gene polymorphism. Out of 27 isolates of P. falciparum, 20 showed formation of rosettes in vitro. The growth rate at 96h varied widely among the isolates. In Pfcrt gene analysis at 76-codon site, 14 showed wild-type Lys 76, 7 showed mutant type Thr 76 and 6 had mixed type. 14 children, all with anaemia on d 7, showed a positive direct antiglobulin test (DAT). Sera positive by ELISA IgG on d 90 also showed parasite growth inhibitory activity in vitro. Significant levels of IgG, IgG1 and IgG3 subclass antibodies against MSP1 were detected in 14 sera collected on d 90. On d 180, there was a decline in IgG and its subtypes. These findings suggest that a variability in isolates may occur in one and the same seasonal area, making children prone to infection. As a consequence, they develop antibodies during recovery phase from an acute attack, which remain in circulation for a period of 4-5 months. After that, a decline in antibody level may again make them susceptible to the disease. Prevalence of different serotypes in a small area may suggest the complexity of malaria transmission. [ABSTRACT FROM AUTHOR]